哮喘联盟

   摘要
   背景：肥胖是哮喘的危险因素，肥胖哮喘患者更可能成为重症且激素不敏感。肥胖如何影响哮喘的发病机制与严重程度尚不清楚。增加的炎性小体介导的中性粒细胞反应，2型免疫和嗜酸性炎症的作用已经被描述。
   目的：研究肥胖如何影响哮喘的发病机制和严重程度，并确定与肥胖相关疾病的有效疗法。
   方法：我们评估了25例哮喘受试者体重指数和痰中炎性小体反应与2型免疫反应之间的关联。在实验性高脂肪饮食诱导的肥胖和哮喘中，研究了NLRP3炎性小体和2型细胞因子反应在驱动疾病关键特征中的功能作用。
   结果：哮喘受试者体重指数和炎症小体反应与痰中IL-5和IL-13表达增加以及C-C趋化因子3型受体表达呈正相关。在存在或缺乏实验性哮喘时，高脂肪饮食诱导的肥胖均可导致激素不敏感的气道高反应性。高脂肪饮食引起的肥胖也与实验哮喘气道组织而不是管腔中增加的NLRP3炎性小体反应和嗜酸性炎症有关。在实验性哮喘中，抑制NLRP3炎性小体反应可降低激素不敏感的气道高反应性，但对IL-5或IL-13反应没有影响。IL-5和IL-13的耗竭可降低实验性哮喘中肥胖引起的NLRP3炎性小体反应和激素不敏感的气道高反应性。
   结论：我们揭示出肥胖型哮喘中2型细胞因子与NLRP3炎性小体反应的关系，突出了2型细胞因子靶向生物制剂和炎性小体抑制剂的潜在效用。
   关键词：哮喘；IL-13；IL-5；NLRP3炎性小体；肥胖。

 

(刘影¹ 张红萍¹ 王刚² 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（J Allergy Clin Immunol. 2021 Oct 19:S0091-6749(21)01525-6. doi:10.1016/j.jaci.2021.10.003.）

 
 
Relationship between type 2 cytokine and inflammasome responses in obesity-associated asthma
 
J Allergy Clin Immunol. 2021 Oct 19:S0091-6749(21)01525-6. doi:10.1016/j.jaci.2021.10.003.
 
Pinkerton JW, Kim RY, Brown AC, Rae BE, Donovan C, Mayall JR, Carroll OR, Ali MK, Scott HA, Berthon BS, Baines KJ, Starkey MR, Kermani NZ, Guo YK, Robertson AAB, O'Neill LAJ, Adcock IM, Cooper MA, Gibson PG, Wood LG, Hansbro PM, Horvat JC.
 
Abstract
Background: Obesity is a risk factor for asthma and obese asthmatics are more likely to have severe, steroid-insensitive disease. How obesity affects the pathogenesis and severity of asthma is poorly understood. Roles for increased inflammasome-mediated neutrophilic responses, type-2 immunity and eosinophilic inflammation have been described.
Objective: To investigate how obesity affects the pathogenesis and severity of asthma and identify effective therapies for obesity-associated disease.
Methods: We assessed associations between body mass index and inflammasome responses with type-2 immune responses in the sputum of 25 subjects with asthma. Functional roles for NLRP3 inflammasome and type-2 cytokine responses in driving key features of disease were examined in experimental high fat diet-induced obesity and asthma.
Results: Body mass index and inflammasome responses positively correlate with increased IL-5 and IL-13 expression, and C-C chemokine receptor type 3 expression in the sputum of subjects with asthma. High fat diet-induced obesity results in steroid-insensitive airway hyper-responsiveness in both the presence and absence of experimental asthma. High fat diet-induced obesity is also associated with increased NLRP3 inflammasome responses and eosinophilic inflammation in airway tissue, but not the lumen in experimental asthma. Inhibition of NLRP3 inflammasome responses reduces steroid-insensitive airway hyper-responsiveness but has no effect on IL-5 or IL-13 responses in experimental asthma. Depletion of IL-5 and IL-13 reduces obesity-induced NLRP3 inflammasome responses and steroid-insensitive airway hyper-responsiveness in experimental asthma.
Conclusion: We show a relationship between type-2 cytokine and NLRP3 inflammasome responses in obesity-associated asthma, highlighting the potential utility of type-2 cytokine-targeted biologics and inflammasome inhibitors.
Keywords: Asthma; IL-13; IL-5; NLRP3 inflammasomes; Obesit